Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells

Carlos E. Rivera, Yulai Zhou, Daniel P. Chupp, Hui Yan, Amanda D. Fisher, Raphael Simon, Hong Zan, Zhenming Xu, Paolo Casali

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Maturation of antibody responses entails somatic hypermutation (SHM), class-switch DNA recombination (CSR), plasma cell differentiation, and generation of memory B cells, and it is thought to require T cell help. We showed that B cell Toll-like receptor 4 (TLR4)–B cell receptor (BCR) (receptor for antigen) coengagement by 4-hydroxy-3-nitrophenyl acetyl (NP)–lipopolysaccharide (LPS) (Escherichia coli lipid A polysaccharide O-antigen) or TLR5-BCR coengagement by Salmonella flagellin induces mature antibody responses to NP and flagellin in Tcrβ/Tcrδ/ and NSG/B mice. TLR-BCR coengagement required linkage of TLR and BCR ligands, “linked coengagement.” This induced B cell CSR/SHM, germinal center–like differentiation, clonal expansion, intraconal diversification, plasma cell differentiation, and an anamnestic antibody response. In Tcrβ/Tcrδ/ mice, linked coengagement of TLR4-BCR by LPS or TLR5-BCR by flagellin induced protective antibodies against E. coli or Salmonella Typhimurium. Our findings unveiled a critical role of B cell TLRs in inducing neutralizing antibody responses, including those to microbial pathogens, without T cell help.

Original languageEnglish (US)
Article numbereade8928
JournalScience Advances
Volume9
Issue number17
DOIs
StatePublished - Apr 2023

ASJC Scopus subject areas

  • General

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